Primary Systemic Amyloidosis
 The Human Immunology & Cancer Program has focused its clinical and research efforts on one particular form of amyloidosis - primary systemic amyloidosis - also referred to as AL amyloidosis.
The proteins associated with this type of amyloid are composed of antibody-related molecules (immunoglobulins) that are involved in the body's defense against infection. They are made by plasma cells in the bone marrow and are secreted into the blood stream. For unknown reasons, a single population or clone of plasma cells grows excessively (such as occurs in multiple myeloma and other conditions). This leads to an increased production and secretion of these proteins, some of which eventually can form amyloid.
Because they result from the proliferation of a single (i.e., monoclonal) plasma cell, the antibodies produced are termed monoclonal immunoglobulins or M-components. One particular type of M-component - Bence Jones protein - was named after its discoverer, Dr. Henry Bence Jones, over 150 years ago. This protein represents a portion of the antibody molecule called the light chain; thus, when this material deposits as amyloid, the resulting condition is designated light-chain or AL amyloidosis.
Features of Primary (AL) Amyloidosis
The primary (AL) form of amyloidosis is relatively uncommon, with an incidence of approximately 1 per 100,000 population; it is estimated that about 2,000-3,000 new cases are diagnosed each year. The disorder typically is manifested during the fifth or sixth decade of life and is apparently non-inheritable. Because it is fairly rare, it is often overlooked as a cause of organ dysfunction until late in the course of the disease.
Tissues that appear to be targeted for AL fibril deposition include kidney, heart, liver, spleen, intestine, tongue, and nerve. Each patient has a particular pattern of organ involvement. In some individuals, the kidney is predominantly affected; in others, kidney function is normal and the heart or some other tissue is damaged. The disease is progressive and ultimately proves fatal within one or two years of diagnosis; however, treatment can often slow the course of illness.
Diagnosis
 Regardless of the organ predominately infiltrated by AL amyloid deposits, this material is typically present in blood vessels throughout the body and can be readily found in Congo red-stained tissue biopsies of kidney or other organs. Often, a simple and relatively painless diagnostic procedure, such as withdrawing a small sample of fat by needle and syringe from under the skin of the abdomen can provide sufficient material for Congo red staining and diagnosis.
Further, abnormal plasma cells occurring in the bone marrow and M-proteins in blood or urine can be readily detected in the laboratory. From the results of these studies, as well as the identification of the type of protein contained in amyloid-laden tissue, the diagnosis of the AL form of amyloidosis can be established.
Other standard medical procedures are used to identify organs suspected of being involved by the amyloid process. These include examination of the heart by echocardiography or liver and spleen by CT or MRI scans. The use of certain radioactive agents may allow the amyloid deposits to be seen. The unequivocal diagnosis of AL amyloidosis cannot be made, however, on the basis of these tests alone. Rather, biopsy of potentially-affected tissues is required.
Treatment
 The treatment of patients with AL amyloidosis is presently limited. The main approach has been to control the disease's symptoms that result, for example, from kidney or heart damage. Much attention has been given to reducing the number of plasma cells and, thus, the amount of M-protein that is eventually deposited as amyloid. This can be accomplished with chemotherapeutic drugs, such as melphalan and prednisone or high-dose dexamethasone, that are also used in multiple myeloma.
In some cases, bone marrow or stem cell transplants have made it possible to achieve this effect since higher doses of chemotherapy can be administered. Such intensive treatment has been associated with prolongation of life, and in some cases, amyloid deposits seemingly are resolved over time; however, patients with heart involvement or the elderly are not candidates for this type of therapy.
Individuals with soft tissue deposits of amyloid have benefited from a drug called IDOX that was developed and tested in Europe. Unfortunately, those with the more common manifestation of heart or kidney deposits are unlikely to improve. In the case of patients whose kidneys have failed due to amyloid deposition and who are on dialysis, a renal transplant offers hope. Cardiac transplantation may be beneficial in rare instances. Overall, however, the prognosis of AL amyloidosis still remains poor.
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